Immediate hypersensitivity reactions result from the activation of mast cells at the interface between the[unreadable] outside environment and tissues such as airways, gastrointestinal tract and skin. IgE antibody binds to[unreadable] mast cells and basophils and upon aggregation of the receptor for IgE antibody, FceRI, the cell is activated[unreadable] to secrete a variety of mediators that cause the local and systemic response characteristic of allergies. It[unreadable] is well accepted that IgE mediates this kind of reaction but translation of this knowledge to the expression[unreadable] of allergic disease is poor. The question addressed in this project is how much IgE is necessary and what[unreadable] parameters adequately predict a response in an individual patient. Indirectly, this project asks whether[unreadable] these parameters alone are sufficient to account for responsiveness in vivo. The first aim directly[unreadable] addresses the issue and posits three critical parameters, IgE density on basophils or mast cells (which is[unreadable] itself regulated by IgE and other factors to be explored), the antigen-specific to total IgE ratio and the[unreadable] basophil (mast cell) sensitivity - a new parameter that is defined as the number of antigen-specific IgE[unreadable] molecules required for a 50% maximum response. A test of the importance of these three parameters is[unreadable] proposed which uses the drug omalizumab in cat allergic patients to manipulate IgE levels into each[unreadable] patients critical response region while measuring basophil and mast cell responses. The second aim[unreadable] focuses on the role of the beta subunit of FceRI on controlling basophil sensitivity to antigen stimulation and[unreadable] FceRI expression. This aim will also propose a manipulation of IgE levels in vivo to optimize changes[unreadable] induced by an experimental allergen challenge in vivo that is expected to alter cytokine levels that control[unreadable] FceRI beta expression. The primary goal is to assess the quantitative rates of receptor expression in vivo.[unreadable] The final two aims are related to aims 1 and 2; they examine the changes in signaling molecule[unreadable] expression during modulation of IgE in vivo and assess the rate of FceRI a synthesis in vivo using a[unreadable] unique method of analysis based on omalizumab-induced decay of FceRI expression.